The mechanism of forskolin activation of thyroid adenylate cyclase has been investigated in detail. The drug is a full agonist of adenylate cyclase and leads to rapid accumulation of cAMP to levels greater than attained with maximal doses of TSH. It stimulates membrane adenylate cyclase without GTP and acts either on the catalytic unit and/or via the unoccupied GTP regulatory protein. It does not change the sensitivity toward other agonists in contrast to other tissues and is more potent in cell-free systems.